Cancer

3 Functional traits ● Uncontrolled and high rate of cell division ● Loss of contact inhibition (continue dividing despite being in contact) ● Loss of anchorage dependence (can divide without attaching to surface) _______________________________________ . 5 Structural traits ● Loss of usual specialised structure ● **Large, And irregularly shaped nuclei, ● small cytoplasmic volume . ● Variation in cell size and shape ● Poorly defined tumour boundaries and disorganised arrangement

it is an accumulation of several independent mutations in cancer-critical genes in a single cell lineage

• define cancer - cancer is the accumulation of several mutations in cancer critical genes in a single cell lineage _______________________________________ • Describe mutations to cancer critical genes - GOF mutation in several protooncogene, in at least one copy - LOF mutation in several TSG in at least two copies _____________________________________ . • telomerase gene - Activation of telomerase expression produces telomerase, which maintains telomere length, - allowing cancer cells to divide indefinitely without reaching the Hayflick limit - NO cell senescence - NO apoptosis ______________________________________ . • angiogenesis - Angiogenesis occurs where growing tumour stimulates formation of new blood vessels - Increased blood flow to tumour supplies more oxygen and nutrients - and removes metabolic waste, promoting tumour growth . - while depleting resources from healthy cells ______________________________________ . • Metastasis - Metastasis occurs where cancer cells enter the circulatory system - and migrate to distant sites to form **secondary tumours*

• loss of fx mutation in BOTH COPIES of p53 gene (TSG) will give rise to p53 protein with altered 3D conformation, becoming non-functional . • Non-functional p53 proteins cannot activate the expression of other genes essential in cell cycle inhibition . • Proteins that repair DNA, arrest cell growth, initiates apoptosis cannot be synthesised - Cell cycle inhibition cannot occur, mutations in DNA are not repaired . • Mutations ACCUMULATE and PASSED DOWN to daughter cells

• RNA pol and transcription factors cannot recognise and bind to the promoter of the p53 gene (TSG) . • p53 protein is NOT synthesised to activate the expression other proteins essential in cell cycle inhibition . • Proteins that repair DNA, arrest cell growth, initiates apoptosis cannot be synthesised_ . • mutations accumulate and are passed down to daughter cells

• GOF mutation in AT LEAST ONE COPY of Ras oncogene will code for ras protein with altered 3D conformation - becoming hyperactive . • Ras protein remains constitutively active with the GTP bound to it - despite lack of the growth factor (ligand) binding to the growth factor receptor . • Signal transduction pathways promoting cell division and proliferation, triggered by ras protein are constitutively switched on . • This leads to overstimulation of the cell cycle and uncontrolled cell division

• Improved recruitment of general transcription factors and RNA polymerase binding to the promoter of ras gene, - causes ras gene expression to increase . • Excess ras proteins are produced, - increasing activation of signal transduction pathways promoting cell division and proliferation . • This leads to overstimulation of the cell cycle and uncontrolled cell division

• Carcinogens in cigarette smoke ● Polycyclic aromatic hydrocarbons_ bind to DNA_ to form adducts, damaging DNA . - increasing error risk in DNA rep - leading to accumulation of mutations in cancer critical genes _______________________________________ . • _ Overexposure to ultraviolet radiation_ ● Leads to **production of covalent attachment between adjacent thymine dimers ● Leads to point mutations in DNA . - increasing error risk in DNA rep - leading to accumulation of mutations in cancer critical genes _______________________________________ . • Ionising radiation (e.g. X-rays, gamma rays) ● Breaks sugar-phosphate backbone - breaks H bonds between base pairs . - increasing error risk in DNA rep - leading to accumulation of mutations in cancer critical genes _______________________________________ . • Genetic predisposition ● Inheritance of one copy of mutated tumour suppressor gene (TSG) or oncogene ● Shorter time /less mutations needed - for enough TSG and oncogene mutations to accumulate - to cause uncontrolled cell division _______________________________________ . • Loss of immunity (e.g. due to HIV, stress, immunosuppressant drugs) ● Lower T cell and B cell count ● Reduces the body’s ability to detect and destroy cancerous cells/ fight infections that may lead to cancer _______________________________________ . • _Viral infections (e.g. HPV) _ ● Virus integrate their genetic material into host cell genome , possibly inactivating TSG/ activating proto-oncogene to oncogene

1) Telomerase’s RNA template complementary base pair with 3’ overhang of the telomere, aligning telomerase reverse transcriptase (TERT) with respect to the DNA ________\____________ 2) Incoming deoxyribonucleotides complementary base pair with the unpaired ribonucleotides of the RNA template. TERT catalyses formation of phosphodiester bond_ between the growing 3’ overhang and the 5’phosphate end of incoming DNA nucleotides ________\____________ 3) Telomerase translocates to the end of the 3’ overhang to continue elongating it with tandem repeat sequence 5’-TTAGGG-3’

S1 - contains many tandem repeats 5’–TTAGGG–3’ . F1 - protect critical coding genes near the end of the chromosome - by eroding in place of the genes _______________________________________ . S2 - 3’ overhang - is single stranded and unreplicated - folds back on itself - hybridises with an earlier comp repeat - to form a T loop - stabilised by telomere binding protein . F2 - protect 3’ overhang from degradation by exonucleases . - stabilise chromosomes, prevent single stranded 3’overhang from fusing w each other . - allow for extension of 3’ overhang by providing specific bindig site for telomerase

1) Activation of telomerase expression produces telomerase, which maintains telomere length, . 2) allowing cancer cells to divide indefinitely without reaching the Hayflick limit